Receiving care according to national heart failure guidelines is associated with lower total costs: an observational study in Region Halland, Sweden.

AIMS: Patients with heart failure (HF) have high costs, morbidity, and mortality, but it is not known if appropriate pharmacotherapy (AP), defined as compliance with international evidence-based guidelines, is associated with improved costs and outcomes. The purpose of this study was to evaluate HF patients' health care utilization, cost and outcomes in Region Halland (RH), Sweden, and if AP was associated with lower costs. METHODS AND RESULTS: A total of 5987 residents of RH in 2016 carried HF diagnoses. Costs were assigned to all health care utilization (inpatient, outpatient, emergency department, primary health care, and medications) using a Patient Encounter Costing methodology. Care of HF patients cost €58.6 M, (€9790/patient) representing 8.7% of RH's total visit expenses and 14.9% of inpatient care (IPC) expenses. Inpatient care represented 57.2% of this expenditure, totalling €33.5 M (€5601/patient). Receiving AP was associated with significantly lower costs, by €1130 per patient (P < 0.001, 95% confidence interval 574-1687). Comorbidities such as renal failure, diabetes, chronic obstructive pulmonary disease, and cancer were significantly associated with higher costs. CONCLUSION: Heart failure patients are heavy users of health care, particularly IPC. Receiving AP is associated with lower costs even adjusting for comorbidities, although causality cannot be proven from an observational study. There may be an opportunity to decrease overall costs and improve outcomes by improving prescribing patterns and associated high-quality care.

Identification of Genes Required for Enzalutamide Resistance in Castration-Resistant Prostate Cancer Cells In Vitro.

Castration-resistant prostate cancer can be treated with the antiandrogen enzalutamide, but responses and duration of response are variable. To identify genes that support enzalutamide resistance, we performed a short hairpin RNA (shRNA) screen in the bone-homing, castration-resistant prostate cancer cell line, C4-2B. We identified 11 genes (TFAP2C, CAD, SPDEF, EIF6, GABRG2, CDC37, PSMD12, COL5A2, AR, MAP3K11, and ACAT1) whose loss resulted in decreased cell survival in response to enzalutamide. To validate our screen, we performed transient knockdowns in C4-2B and 22Rv1 cells and evaluated cell survival in response to enzalutamide. Through these studies, we validated three genes (ACAT1, MAP3K11, and PSMD12) as supporters of enzalutamide resistance in vitro Although ACAT1 expression is lower in metastatic castration-resistant prostate cancer samples versus primary prostate cancer samples, knockdown of ACAT1 was sufficient to reduce cell survival in C4-2B and 22Rv1 cells. MAP3K11 expression increases with Gleason grade, and the highest expression is observed in metastatic castration-resistant disease. Knockdown of MAP3K11 reduced cell survival, and pharmacologic inhibition of MAP3K11 with CEP-1347 in combination with enzalutamide resulted in a dramatic increase in cell death. This was associated with decreased phosphorylation of AR-Serine650, which is required for maximal AR activation. Finally, although PSMD12 expression did not change during disease progression, knockdown of PSMD12 resulted in decreased AR and AR splice variant expression, likely contributing to the C4-2B and 22Rv1 decrease in cell survival. Our study has therefore identified at least three new supporters of enzalutamide resistance in castration-resistant prostate cancer cells in vitro.

Regulatory and Safety Considerations in Deploying a Locally Fabricated, Reusable Face Shield in a Hospital Responding to the COVID-19 Pandemic.

BACKGROUND: Due to supply chain disruption, the COVID-19 pandemic has caused severe shortages in personal protective equipment for health care professionals. Local fabrication based on 3D printing is one way to address this challenge, particularly in the case of products such as protective face shields. No clear path exists, however, for introducing a locally fabricated product into a clinical setting. METHODS: We describe a research protocol under Institutional Review Board supervision that allowed clinicians to participate in an iterative design process followed by real-world testing in an emergency department. All designs, materials used, testing protocols, and survey results are reported in full to facilitate similar efforts in other clinical settings. FINDINGS: Clinical testing allowed the incident command team at a major academic medical center to introduce the locally fabricated face shield into general use in a rapid but well-controlled manner. Unlike standard hospital face shields, the locally fabricated design was intended to be reusable. We discuss the design and testing process and provide an overview of regulatory considerations associated with fabrication and testing of personal protective equipment, such as face shields. CONCLUSIONS: Our work serves as a case study for robust, local responses to pandemic-related disruption of medical supply chains with implications for health care professionals, hospital administrators, regulatory agencies, and concerned citizens in the COVID-19 and future health care emergencies. FUNDING: : This work was supported by the Harvard MIT Center for Regulatory Sciences, NIH/NCI grants U54-CA225088 and T32-GM007753, and the Harvard Ludwig Center. M.-J.A. is a Friends of McGovern Graduate Fellow.

Rapid prototyping and clinical testing of a reusable face shield for health care workers responding to the COVID-19 pandemic.

Due to supply chain disruption, the COVID-19 pandemic has caused severe shortages in personal protective equipment (PPE) for health care professionals. Local fabrication based on 3D printing is one way to address this challenge, particularly in the case of simple products such as protective face shields. As a consequence, many public domain designs for face shields have become available. No clear path exists, however, for introducing a locally fabricated and unapproved product into a clinical setting. In a US health care setting, face shields are regulated by the Food and Drug Administration (FDA); similar policies exist in other countries. We describe a research protocol under which rapid iteration on an existing design, coupled with clinical feedback and real-world testing in an emergency department, allowed a face shield to be adopted by the incident command team at a major academic medical center. We describe our design and testing process and provide an overview of regulatory considerations associated with fabrication and testing of face shields and related products. All designs, materials used, testing protocols, and survey results are reported in full to facilitate the execution of similar face shield efforts in other clinical settings. Our work serves as a case study for development of a robust local response to pandemics and other health care emergencies, with implications for healthcare professionals, hospital administrators, regulatory agencies and concerned citizens.

Training machine learning models to predict 30-day mortality in patients discharged from the emergency department: a retrospective, population-based registry study.

OBJECTIVES: The aim of this work was to train machine learning models to identify patients at end of life with clinically meaningful diagnostic accuracy, using 30-day mortality in patients discharged from the emergency department (ED) as a proxy. DESIGN: Retrospective, population-based registry study. SETTING: Swedish health services. PRIMARY AND SECONDARY OUTCOME MEASURES: All cause 30-day mortality. METHODS: Electronic health records (EHRs) and administrative data were used to train six supervised machine learning models to predict all-cause mortality within 30 days in patients discharged from EDs in southern Sweden, Europe. PARTICIPANTS: The models were trained using 65 776 ED visits and validated on 55 164 visits from a separate ED to which the models were not exposed during training. RESULTS: The outcome occurred in 136 visits (0.21%) in the development set and in 83 visits (0.15%) in the validation set. The model with highest discrimination attained ROC-AUC 0.95 (95% CI 0.93 to 0.96), with sensitivity 0.87 (95% CI 0.80 to 0.93) and specificity 0.86 (0.86 to 0.86) on the validation set. CONCLUSIONS: Multiple models displayed excellent discrimination on the validation set and outperformed available indexes for short-term mortality prediction interms of ROC-AUC (by indirect comparison). The practical utility of the models increases as the data they were trained on did not require costly de novo collection but were real-world data generated as a by-product of routine care delivery.

Hospital ward transfer to intensive care unit as a quality marker in emergency medicine.

BACKGROUND: Minimizing and preventing adverse events and medical errors in the emergency department (ED) is an ongoing area of quality improvement. Identifying these events remains challenging. OBJECTIVE: To investigate the utility of tracking patients transferred to the ICU within 24h of admission from the ED as a marker of preventable errors and adverse events. METHODS: From November 2011 through June 2016, we prospectively collected data for all patients presenting to an urban, tertiary care academic ED. We utilized an automated electronic tracking system to identify ED patients who were admitted to a hospital ward and then transferred to the ICU within 24h. Reviewers screened for possible error or adverse event and if discovered the case was referred to the departmental Quality Assurance (QA) committee for deliberations and consensus agreement. RESULTS: Of 96,377 ward admissions, 921 (1%) patients were subsequently transferred to the ICU within 24h of ED presentation. Of these 165 (19%) were then referred to the QA committee for review. Total rate of adverse events regardless of whether or not an error occurred was 2.1%, 19/921 (95% CI 1.4% to 3.0%). Medical error on the part of the ED was 2.2%, 20/921 (95% CI 1.5% to 3.1%) and ED Preventable Error in 1.1%, 10/921 (95% CI 0.6% to 1.8%). CONCLUSION: Tracking patients admitted to the hospital from the ED who are transferred to the ICU <24h after admission may be a valuable marker for adverse events and preventable errors in the ED.

Ethnographic analysis on the use of the electronic medical record for clinical handoff.

The objective of this study was to understand the social elements of clinical and organizational interactions of the key stakeholders in the specific context of an electronic dashboard used by the emergency department (ED) and inpatient medicine teams at the time of clinical referral and handover. An electronic handover function is utilised at the ED-inpatient interface at this institution and has given clinicians the ability to better communicate, monitor the department and strive to improve patient safety in streamline the delivery of care in the acute phase. This study uses an ethnographic qualitative research design incorporating semistructured interviews, participant observation on the ED floor and fieldwork notes. The setting for this research was in the ED at a tertiary University affiliated hospital. Triangulation was used to combine information obtained from multiple sources and information from fieldwork and interviews refined into useable chunks culminating in a thematic analysis. Thematic analysis yielded five central themes that reflected how the clinical staff utilised this IT system and why it had become embedded in the culture of clinical referral and handover. Efficient time management for improved patient flow was demonstrated, value added communication (at the interpersonal level), the building trust at the ED-inpatient interface, the maintenance of mutual respect across medical cultures and an overall enhancement of the quality of ED communication (in terms of the information available). A robust electronic handover process, resulted in an integrated approach to patient care by removing barriers to admission for medical inpatients, admitted via ED. The value proposition for patients was a more complete information transfer, both within the ED and between departments.

Nfib Regulates Transcriptional Networks That Control the Development of Prostatic Hyperplasia.

A functional complex consisting of androgen receptor (AR) and forkhead box A1 (FOXA1) proteins supports prostatic development, differentiation, and disease. In addition, the interaction of FOXA1 with cofactors such as nuclear factor I (NFI) family members modulates AR target gene expression. However, the global role of specific NFI family members has yet to be described in the prostate. In these studies, chromatin immunoprecipitation followed by DNA sequencing in androgen-dependent LNCaP prostate cancer cells demonstrated that 64.3% of NFIB binding sites are associated with AR and FOXA1 binding sites. Interrogation of published data revealed that genes associated with NFIB binding sites are predominantly induced after dihydrotestosterone treatment of LNCaP cells, whereas NFIB knockdown studies demonstrated that loss of NFIB drives increased AR expression and superinduction of a subset of AR target genes. Notably, genes bound by NFIB only are associated with cell division and cell cycle. To define the role of NFIB in vivo, mouse Nfib knockout prostatic tissue was rescued via renal capsule engraftment. Loss of Nfib expression resulted in prostatic hyperplasia, which did not resolve in response to castration, and an expansion of an intermediate cell population in a small subset of grafts. In human benign prostatic hyperplasia, luminal NFIB loss correlated with more severe disease. Finally, some areas of intermediate cell expansion were also associated with NFIB loss. Taken together, these results show a fundamental role for NFIB as a coregulator of AR action in the prostate and in controlling prostatic hyperplasia.

PIM kinase inhibitor AZD1208 for treatment of MYC-driven prostate cancer.

BACKGROUND: PIM1 kinase is coexpressed with c-MYC in human prostate cancers (PCs) and dramatically enhances c-MYC-induced tumorigenicity. Here we examine the effects of a novel oral PIM inhibitor, AZD1208, on prostate tumorigenesis and recurrence. METHODS: A mouse c-MYC/Pim1-transduced tissue recombination PC model, Myc-CaP allografts, and human PC xenografts were treated with AZD1208 (n = 5-11 per group). Androgen-sensitive and castrate-resistant prostate cancer (CRPC) models were studied as well as the effects of hypoxia and radiation. RNA sequencing was used to analyze drug-induced gene expression changes. Results were analyzed with χ(2) test. Student's t test and nonparametric Mann-Whitney rank sum U Test. All statistical tests were two-sided. RESULTS: AZD1208 inhibited tumorigenesis in tissue recombinants, Myc-CaP, and human PC xenograft models. PIM inhibition decreased c-MYC/Pim1 graft growth by 54.3 ± 39% (P < .001), decreased cellular proliferation by 46 ± 14% (P = .016), and increased apoptosis by 326 ± 170% (P = .039). AZD1208 suppressed multiple protumorigenic pathways, including the MYC gene program. However, it also downregulated the p53 pathway. Hypoxia and radiation induced PIM1 in prostate cancer cells, and AZD1208 functioned as a radiation sensitizer. Recurrent tumors postcastration responded transiently to either AZD1208 or radiation treatment, and combination treatment resulted in more sustained inhibition of tumor growth. Cell lines established from recurrent, AZD1208-resistant tumors again revealed downregulation of the p53 pathway. Irradiated AZD1208-treated tumors robustly upregulated p53, providing a possible mechanistic explanation for the effectiveness of combination therapy. Finally, an AZD1208-resistant gene signature was found to be associated with biochemical recurrence in PC patients. CONCLUSIONS: PIM inhibition is a potential treatment for MYC-driven prostate cancers including CRPC, and its effectiveness may be enhanced by activators of the p53 pathway, such as radiation.

NFI transcription factors interact with FOXA1 to regulate prostate-specific gene expression.

Androgen receptor (AR) action throughout prostate development and in maintenance of the prostatic epithelium is partly controlled by interactions between AR and forkhead box (FOX) transcription factors, particularly FOXA1. We sought to identity additional FOXA1 binding partners that may mediate prostate-specific gene expression. Here we identify the nuclear factor I (NFI) family of transcription factors as novel FOXA1 binding proteins. All four family members (NFIA, NFIB, NFIC, and NFIX) can interact with FOXA1, and knockdown studies in androgen-dependent LNCaP cells determined that modulating expression of NFI family members results in changes in AR target gene expression. This effect is probably mediated by binding of NFI family members to AR target gene promoters, because chromatin immunoprecipitation (ChIP) studies found that NFIB bound to the prostate-specific antigen enhancer. Förster resonance energy transfer studies revealed that FOXA1 is capable of bringing AR and NFIX into proximity, indicating that FOXA1 facilitates the AR and NFI interaction by bridging the complex. To determine the extent to which NFI family members regulate AR/FOXA1 target genes, motif analysis of publicly available data for ChIP followed by sequencing was undertaken. This analysis revealed that 34.4% of peaks bound by AR and FOXA1 contain NFI binding sites. Validation of 8 of these peaks by ChIP revealed that NFI family members can bind 6 of these predicted genomic elements, and 4 of the 8 associated genes undergo gene expression changes as a result of individual NFI knockdown. These observations suggest that NFI regulation of FOXA1/AR action is a frequent event, with individual family members playing distinct roles in AR target gene expression.

RAMP1 is a direct NKX3.1 target gene up-regulated in prostate cancer that promotes tumorigenesis.

The homeodomain-containing transcription factor, NKX3.1, plays an important role in the suppression of prostate tumorigenesis. Herein, we identify the receptor activity-modifying protein 1 (RAMP1) as a direct NKX3.1 target gene through analysis of chromatin immunoprecipitation coupled to massively parallel sequencing and gene expression data. RAMP1 is a coreceptor for certain G-protein-coupled receptors, such as the calcitonin gene-related peptide receptor, to the plasma membrane. We found that RAMP1 expression is specifically elevated in human prostate cancer relative to other tumor types. Furthermore, RAMP1 mRNA and protein levels are significantly higher in human prostate cancer compared with benign glands. We identified multiple NKX3.1 binding sites in the RAMP1 locus in human prostate cancer cells and in the normal mouse prostate. Analyses of Nkx3.1 knockout mice and human prostate cancer cell lines indicate that NKX3.1 represses RAMP1 expression. Knockdown of RAMP1 by shRNA decreased prostate cancer cell proliferation and tumorigenicity in vitro and in vivo. By using gene expression profiling and pathway analyses, we identified several cancer-related pathways that are significantly altered in RAMP1 knockdown cells, including the mitogen-activated protein kinase signaling pathway. Further experiments confirmed a reduction in MAP2KI (MEK1) expression and phosphorylated-extracellular signal-regulated kinase 1/2 levels in RAMP1 knockdown cells. These data provide novel insights into the role of RAMP1 in promoting prostate tumorigenesis and support the potential of RAMP1 as a novel biomarker and possible therapeutic target in prostate cancer.

National survey of emergency departments in Denmark.

OBJECTIVES: Emergency departments (EDs) are the basic unit of emergency medicine, but often differ in fundamental features. We sought to describe and characterize EDs in Denmark. METHODS: All EDs open 24/7 to the general public were surveyed using the National ED Inventories survey instrument (http://www.emnet-nedi.org). ED staff were asked about ED characteristics with reference to the calendar year 2008. RESULTS: Twenty-eight EDs participated (82% response). All were located in hospitals. Less than half [43%, 95% confidence interval (CI) 24-63%] were independent departments. Thirty-nine percent (95% CI 22-59%) had a contiguous layout, with medical and surgical care provided in one area. The vast majority of EDs saw both adults and children; only 10% saw adults only and none saw children only. The median number of annual visits was 32 000 (interquartile range, 14 700-47 000). The majority (68%, 95% CI 47-89%) believed that their ED was at good balance or capacity, with 22% responding that they were under capacity and 9% reporting overcapacity. Technological resources were generally available, with the exception of dedicated computed tomography scanners and negative-pressure rooms. Almost all common emergencies were identified as being treatable 24/7 in the EDs. CONCLUSION: Although there is some variation in their layout and characteristics, most Danish EDs have a high degree of resource availability and are able to treat common emergencies. As Denmark seeks to reform emergency care through ED consolidation, this national survey helps to establish a benchmark for future comparisons.

Antioxidant treatment promotes prostate epithelial proliferation in Nkx3.1 mutant mice.

Discordant results in preclinical and clinical trials have raised questions over the effectiveness of antioxidants in prostate cancer chemoprevention. Results from the large-scale Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed that antioxidants failed to prevent, and in some cases promoted, prostate cancer formation in men without a history of the disease. One possible explanation for these alarming results is the notion that the effects of antioxidant treatment on the prostate are modified by specific, intrinsic genetic risk factors, causing some men to respond negatively to antioxidant treatment. Loss of expression of the homeobox transcription factor NKX3.1 in the prostate is frequently associated with human prostate cancer. Nkx3.1 mutant mice display prostatic hyperplasia and dysplasia and are used as a model of the early stages of prostate cancer initiation. While the mechanisms by which Nkx3.1 loss promotes prostate tumorigenicity are not completely understood, published data have suggested that elevated reactive oxygen species (ROS) associated with Nkx3.1 loss may be a causative factor. Here we have tested this hypothesis by treating Nkx3.1 mutant mice with the antioxidant N-acetylcysteine (NAC) for 13 weeks post-weaning. Surprisingly, while NAC treatment decreased ROS levels in Nkx3.1 mutant mouse prostates, it failed to reduce prostatic epithelial hyperplasia/dysplasia. Rather, NAC treatment increased epithelial cell proliferation and promoted the expression of a pro-proliferative gene signature. These results show that ROS do not promote proliferation in the Nkx3.1-null prostate, but instead inhibit proliferation, suggesting that antioxidant treatment may encourage prostate epithelial cell proliferation early in prostate tumorigenesis. Our findings provide new insight that may help explain the increased prostate cancer risk observed with vitamin E treatment in the SELECT trial and emphasize the need for preclinical studies using accurate models of cancer.

Nkx3.1 and Myc crossregulate shared target genes in mouse and human prostate tumorigenesis.

Cooperativity between oncogenic mutations is recognized as a fundamental feature of malignant transformation, and it may be mediated by synergistic regulation of the expression of pro- and antitumorigenic target genes. However, the mechanisms by which oncogenes and tumor suppressors coregulate downstream targets and pathways remain largely unknown. Here, we used ChIP coupled to massively parallel sequencing (ChIP-seq) and gene expression profiling in mouse prostates to identify direct targets of the tumor suppressor Nkx3.1. Further analysis indicated that a substantial fraction of Nkx3.1 target genes are also direct targets of the oncoprotein Myc. We also showed that Nkx3.1 and Myc bound to and crossregulated shared target genes in mouse and human prostate epithelial cells and that Nkx3.1 could oppose the transcriptional activity of Myc. Furthermore, loss of Nkx3.1 cooperated with concurrent overexpression of Myc to promote prostate cancer in transgenic mice. In human prostate cancer patients, dysregulation of shared NKX3.1/MYC target genes was associated with disease relapse. Our results indicate that NKX3.1 and MYC coregulate prostate tumorigenesis by converging on, and crossregulating, a common set of target genes. We propose that coregulation of target gene expression by oncogenic/tumor suppressor transcription factors may represent a general mechanism underlying the cooperativity of oncogenic mutations during tumorigenesis.

World Health Assembly Resolution 60.22 and its importance as a health care policy tool for improving emergency care access and availability globally.

The recent adoption of World Health Assembly Resolution 60.22, titled "Health Systems: Emergency Care Systems," has established an important health care policy tool for improving emergency care access and availability globally. The resolution highlights the role that strengthened emergency care systems can play in reducing the increasing burden of disease from acute illness and injury in populations across the socioeconomic spectrum and calls on governments and the World Health Organization to take specific and concrete actions to make this happen. This resolution constitutes recognition by the World Health Assembly of the growing public health role of emergency care systems and is the highest level of international attention ever devoted to emergency care systems worldwide. Emergency care systems for secondary prevention of acute illnesses and injury remain inadequately developed in many low- and middle-income countries, despite evidence that basic strategies for improving emergency care systems can reduce preventable mortality and morbidity and can in many cases also be cost-effective. Emergency care providers and their professional organizations have used their comprehensive expertise to strengthen emergency care systems worldwide through the development of tools for emergency medicine education, systems assessment, quality improvement, and evidence-based clinical practice. World Health Assembly 60.22 represents a unique opportunity for emergency care providers and other advocates for improved emergency care to engage with national and local health care officials and policymakers, as well as with the World Health Organization, and leverage the expertise within the international emergency medicine community to make substantial improvements in emergency care delivery in places where it is most needed.

International perspectives on emergency department crowding.

The maturation of emergency medicine (EM) as a specialty has coincided with dramatic increases in emergency department (ED) visit rates, both in the United States and around the world. ED crowding has become a public health problem where periodic supply and demand mismatches in ED and hospital resources cause long waiting times and delays in critical treatments. ED crowding has been associated with several negative clinical outcomes, including higher complication rates and mortality. This article describes emergency care systems and the extent of crowding across 15 countries outside of the United States: Australia, Canada, Denmark, Finland, France, Germany, Hong Kong, India, Iran, Italy, The Netherlands, Saudi Arabia, Catalonia (Spain), Sweden, and the United Kingdom. The authors are local emergency care leaders with knowledge of emergency care in their particular countries. Where available, data are provided about visit patterns in each country; however, for many of these countries, no national data are available on ED visits rates or crowding. For most of the countries included, there is both objective evidence of increases in ED visit rates and ED crowding and also subjective assessments of trends toward higher crowding in the ED. ED crowding appears to be worsening in many countries despite the presence of universal health coverage. Scandinavian countries with robust systems to manage acute care outside the ED do not report crowding is a major problem. The main cause for crowding identified by many authors is the boarding of admitted patients, similar to the United States. Many hospitals in these countries have implemented operational interventions to mitigate crowding in the ED, and some countries have imposed strict limits on ED length of stay (LOS), while others have no clear plan to mitigate crowding. An understanding of the causes and potential solutions implemented in these countries can provide a lens into how to mitigate ED crowding in the United States through health policy interventions and hospital operational changes.

The efficacy and value of emergency medicine: a supportive literature review.

STUDY OBJECTIVES: The goal of this study was to identify publications in the medical literature that support the efficacy or value of Emergency Medicine (EM) as a medical specialty and of clinical care delivered by trained emergency physicians. In this study we use the term "value" to refer both to the "efficacy of clinical care" in terms of achieving desired patient outcomes, as well as "efficiency" in terms of effective and/or cost-effective utilization of healthcare resources in delivering emergency care. A comprehensive listing of publications describing the efficacy or value of EM has not been previously published. It is anticipated that the accumulated reference list generated by this study will serve to help promote awareness of the value of EM as a medical specialty, and acceptance and development of the specialty of EM in countries where EM is new or not yet fully established. METHODS: The January 1995 to October 2010 issues of selected journals, including the EM journals with the highest article impact factors, were reviewed to identify articles of studies or commentaries that evaluated efficacy, effectiveness, and/or value related to EM as a specialty or to clinical care delivered by EM practitioners. Articles were included if they found a positive or beneficial effect of EM or of EM physician-provided medical care. Additional articles that had been published prior to 1995 or in other non-EM journals already known to the authors were also included. RESULTS: A total of 282 articles were identified, and each was categorized into one of the following topics: efficacy of EM for critical care and procedures (31 articles), efficacy of EM for efficiency or cost of care (30 articles), efficacy of EM for public health or preventive medicine (34 articles), efficacy of EM for radiology (11 articles), efficacy of EM for trauma or airway management (27 articles), efficacy of EM for using ultrasound (56 articles), efficacy of EM faculty (34 articles), efficacy of EM residencies (24 articles), and overviews and editorials of EM efficacy and value (35 articles). CONCLUSION: There is extensive medical literature that supports the efficacy and value for both EM as a medical specialty and for emergency patient care delivered by trained EM physicians.

Isolation of epiblast stem cells from preimplantation mouse embryos.

Pluripotent stem cells provide a platform to interrogate control elements that function to generate all cell types of the body. Despite their utility for modeling development and disease, the relationship of mouse and human pluripotent stem cell states to one another remains largely undefined. We have shown that mouse embryonic stem (ES) cells and epiblast stem cells (EpiSCs) are distinct, pluripotent states isolated from pre- and post-implantation embryos respectively. Human ES cells are different than mouse ES cells and share defining features with EpiSCs, yet are derived from pre-implantation human embryos. Here we show that EpiSCs can be routinely derived from pre-implantation mouse embryos. The preimplantation-derived EpiSCs exhibit molecular features and functional properties consistent with bona fide EpiSCs. These results provide a simple method for isolating EpiSCs and offer direct insight into the intrinsic and extrinsic mechanisms that regulate the acquisition of distinct pluripotent states.

Precordial steering wheel: a fortunate accident.

BACKGROUND: Myocardial ischemia has been associated with motor vehicle collisions (MVCs). However, we were unable to find reported cases of ST-segment elevation myocardial infarction (STEMI) leading to ventricular tachyarrhythmia and subsequent MVC. In such patients, decisions regarding antiplatelet and antithrombotic therapy need to balance the risk of ongoing myocardial ischemia and hemorrhage. OBJECTIVES: To describe a case of STEMI and ventricular fibrillation (VF) associated with a head-on MVC, and to describe the management decisions involved in the care of such a patient. CASE REPORT: A 47-year-old man presented to the Emergency Department after a single-car head-on collision with a wall at high speed. He had a facial degloving injury as well as right-sided flail chest. An electrocardiogram demonstrated ST-segment elevation in the inferior and anterior leads. Due to the patient's significant traumatic injuries, he underwent a rapid trauma evaluation and was transferred for emergent cardiac catheterization, which demonstrated evidence of plaque rupture in the right coronary artery (RCA). Flow distal to the lesion was preserved, so stent implantation was initially deferred out of concern for hemorrhage secondary to the aggressive antiplatelet and antithrombotic regimen requisite with stent implantation. The patient then went into VF in the cardiac catheterization laboratory, and repeat angiography demonstrated an occluded RCA, and the patient underwent successful stent implantation. CONCLUSION: The management of STEMI in the setting of trauma is complex. Pharmacologic agents used in STEMI increase the risk of bleeding, and management must balance the risk of prolonged ischemia with the risk of hemorrhage.